insulin-glulisine and Weight-Gain

To evaluate the efficacy and safety of adding a single bolus dose of insulin glulisine to basal insulin ('basal-plus') in persons with type 2 diabetes.. Data from patients with poor glycemic control on oral antihyperglycemic drugs who were initiated on a 'basal-plus' regimen for up to 6 months were pooled from four randomized, multicenter studies. Glycated hemoglobin (HbA1c), fasting blood glucose, postprandial glucose (PPG), insulin dose and demographics were measured at baseline and end of study.. 711 patients with a mean age of 59.9 years and a mean duration of diabetes of 11.0 years were included in the analysis population. A 'basal-plus' regimen was associated with significant decreases in HbA1c and PPG at 6 months, an increase in glargine and glulisine doses and small, but statistically significant, changes in body weight and BMI in all patient subsets. The proportion of patients with HbA1c<7% also increased in all populations studied, while the prevalence of severe hypoglycemia was low and did not significantly differ across patient groups.. These results suggest that the use of 'basal-plus' can achieve a good therapeutic response with a low risk of hypoglycemia and weight gain, regardless of a patient's age or BMI.

Topics: Age Factors; Aged; Biomarkers; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

This study investigated the cost per responder and number needed to treat (NNT) in type 2 diabetes mellitus (T2DM) patients for lixisenatide compared to insulin intensification regimens using composite endpoints in the UK, Italy, and Spain.. Efficacy and safety outcomes were obtained from GetGoal Duo-2, a 26-week phase 3 trial comparing lixisenatide vs insulin glulisine (IG) once daily (QD) and three times daily (TID). Response at week 26 was extrapolated to 52 weeks, assuming a maintained treatment effect, based on long-term evidence in other T2DM populations. Responders were defined using composite end-points, based on an HbA1c threshold and/or no weight gain and/or no hypoglycemia. The HbA1c threshold was varied in sensitivity analyses. Annual treatment costs were estimated in euros (1 GBP = 1.26 EUR), including drug acquisition and resource use costs. Cost per responder was computed by dividing annual treatment costs per patient by the proportion of responders.. Lixisenatide was associated with the lowest cost per responder for all composite end-points that included a weight-related component. For the main composite end-point of HbA1c ≤7.5% AND no weight gain AND no symptomatic hypoglycemia, cost per responder results were: UK: 6,867€, 8,746€, and 12,410€; Italy: 7,057€, 9,160€, and 12,844€; Spain: 8,370€, 11,365€, and 17,038€, for lixisenatide, IG QD, and TID, respectively. The NNT analysis showed that, for every 6.85 and 5.86 patients treated with lixisenatide, there was approximately one additional responder compared to IG QD and TID, respectively.. A limitation of the clinical inputs is the lack of 52-week trial data from GetGoal Duo-2, which led to the assumption of a maintained treatment effect from week 26 to 52.. This analysis suggests lixisenatide is an efficient economic resource allocation in the UK, Italy, and Spain.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Fees, Pharmaceutical; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Italy; Models, Econometric; Peptides; Spain; United Kingdom; Weight Gain

Insulin therapy is commonly associated with weight gain. The timing of prandial insulin administration may enhance its efficacy/safety and maintain effective weight control. This study examined the effect of postprandial vs. preprandial insulin glulisine on weight gain and glycaemic control in type 2 diabetes patients taking basal insulin.. This was a multicenter, randomized, open-label trial conducted in 45 centres in the USA. A total of 716 patients with type 2 diabetes and glycated haemoglobin A(1c) (HbA(1c) ) ≥ 7.5% and ≤10.0% were screened; 345 were randomized and 322 comprised the intent-to-treat group (premeal, 163; postmeal, 159). Insulin glargine once daily, ±metformin and subcutaneous injections of premeal or postmeal insulin glulisine were given for 52 weeks. Main outcome measures included changes in HbA(1c) , fasting plasma glucose and weight from study baseline to endpoint (week 52).. At study end, insulin glulisine achieved similar glycaemic control whether it was administered before or after meals (HbA(1c) : 7.04% premeal vs. 7.16% postmeal, p = NS). Overall hypoglycaemia incidence and severe hypoglycaemia rates were not significantly different between premeal and postmeal groups; however, symptomatic and nocturnal hypoglycaemia rates were higher in the postprandial group. Mean body weight was lower in the postmeal group, with the difference between postmeal and premeal weight change from baseline to week 52 of -0.87 kg (p = 0.243).. Postprandial glulisine administration provided similar glycaemic control and was non-inferior to preprandial administration on weight gain, without additional risk of severe hypoglycaemia, showing dosing flexibility and the feasibility of such approach when clinically indicated.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Postprandial Period; Treatment Outcome; Weight Gain

To investigate whether the addition of a single bolus of insulin glulisine (glulisine), administered at either breakfast or main mealtime, in combination with basal insulin glargine (glargine) and oral antidiabetic drugs (OADs), provides equivalent glycaemic control in patients with type 2 diabetes, irrespective of the time of glulisine injection.. A national, multicentre, randomized, open-label, parallel-group study of 393 patients with type 2 diabetes who were suboptimally controlled [haemoglobin A(1c) (HbA(1c)) > 6.5-9.0% and fasting blood glucose (BG) 7.0% at baseline and who reached HbA(1c)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Time Factors; Treatment Outcome; Weight Gain; Young Adult

Topics: Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Male; Middle Aged; Peptides; Weight Gain